E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of cataplexy in narcolepsy Treatment of excessive daytime sleepiness (EDS) in narcolepsy |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10015595 |
E.1.2 | Term | Excessive daytime sleepiness |
E.1.2 | System Organ Class | 100000004852 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007738 |
E.1.2 | Term | Cataplexy and narcolepsy |
E.1.2 | System Organ Class | 100000004852 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of JZP-258 in the treatment of cataplexy in subjects with narcolepsy |
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E.2.2 | Secondary objectives of the trial |
Key Secondary Objective • To evaluate the efficacy of JZP-258 in the treatment of excessive daytime sleepiness (EDS) in subjects with narcolepsy .
Secondary Objective • To evaluate the safety of JZP-258 in the treatment of subjects with narcolepsy with cataplexy
Exploratory Objective • To characterize the conversion from non-Xyrem anticataplectic treatment regimens to JZP-258 in subjects with narcolepsy with cataplexy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Main Study 1.Male or female subjects between 18 and 70 years of age, inclusive at screening. 2.Have a primary diagnosis of narcolepsy with cataplexy that meets International Classification of Sleep Disorders-third edition (ICSD-3) criteria or Diagnostic and Statistical Manual-Fifth Edition (DSM-5) criteria, and currently untreated or treated with or without anticataplectics. 3.Have a history of having at least 14 cataplexy attacks in a typical 2-week period and clinically significant symptoms of EDS prior to any narcolepsy treatment 4.Treatment status (Pre-randomization Group) at study entry: a)Have been taking Xyrem at unchanged doses (twice or thrice nightly dosing no higher than a total of 9 g/night), for the treatment of cataplexy in narcolepsy for at least 2 months prior to screening; or b)Have been taking Xyrem at unchanged doses (twice or thrice nightly dosing no higher than a total of 9 g/night), and another anticataplectic (tricyclic antidepressant [TCA], serotonin-norepinephrine reuptake inhibitor [SNRI], selective serotonin reuptake inhibitor [SSRI], atomoxetine, or other) for the treatment of cataplexy in narcolepsy for at least 2 months prior to screening; or c)Treated with a non-Xyrem anticataplectic (TCA, SNRI, SSRI, atomoxetine, or other) and not treated with Xyrem; or d)Not treated with any agent with anticataplectic properties. 5.If currently treated with Xyrem, must have documented clinical improvement of cataplexy and EDS per Investigator’s clinical judgment. 6.If applicable, treated with a stimulant or alerting agent at unchanged doses for at least 2 months prior to dosing or not treated with a stimulant or alerting agent. 7.Have used a medically acceptable method of contraception for at least 2 months prior to the first dose of study drug and consent to use a medically acceptable method of contraception throughout the entire study period and for 90 days after the study is completed. 8.Willing and able to comply with the study design schedule and other requirements. 9.Willing and able to provide written informed consent. Open Label 1.Completion of the JZP-258 double-blind treatment and completion of Visit 16 2.Is able, in the opinion of the investigator, to take JZP-258 for an additional 24 weeks 3.Agrees to continue to use a medically acceptable method of contraception throughout the entire study period and for 90 days after the Open-Label Extension is completed. 4.Willing and able to comply with the study design schedule and other requirements. 5.Willing and able to provide written informed consent for Open-Label Extension. 6.If currently being treated with Xyrem, the subject’s total twice nightly Xyrem dose must be no higher than 9 g/night
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E.4 | Principal exclusion criteria |
Main Study 1.Narcolepsy secondary to another medical condition (e.g., central nervous system injury or lesion). 2.Restless leg syndrome (RLS) requiring treatment other than iron supplements. 3.Succinic semi-aldehyde dehydrogenase deficiency (SSADH). 4.Uncontrolled hypothyroidism. 5.History of seizures, excluding early childhood non-pathological febrile seizures. 6.History of head trauma associated with loss of consciousness in the past 5 years or if the event occurred more than 5 years prior to screening and the subject has sequelae due to the event. 7.Evidence of untreated or inadequately treated sleep-disordered breathing including: a.Presence of clinically significant and untreated obstructive or central sleep apnea as determined by the Investigator or documented previously; or documentation of one of the following: b.Apnea index (AI) >10 if on obstructive sleep apnea (OSA) treatment or untreated; or c.Clinically significant hypoventilation; or d.Noncompliance with primary OSA therapy. (Compliance defined as positive airway pressure use of ≥4 hours per night on ≥70% of nights [≥5 of 7 nights/week], historical report [with Investigator concurrence] of use of an oral appliance on ≥70% of nights [≥5 of 7 nights/week], or receipt of an effective surgical intervention for OSA symptoms.) 8.Parasomnias (e.g., sleep walking, rapid eye movement [REM] Sleep Behavior Disorder, etc.) felt by the investigator to negatively affect the conduct of the study. Parasomnia events associated with physical injury to the subject (or others) shall be discussed with the Medical Monitor. 9.Meets criteria for current major depression by clinical interview. 10.Any other clinically relevant medical, behavioral, or psychiatric disorder other than narcolepsy that is associated with excessive sleepiness. 11.History or presence of bipolar disorder, bipolar related disorders, schizophrenia, schizophrenia spectrum disorders, or other psychotic disorders according to DSM-5 criteria. 12.History or presence of any unstable or clinically significant medical condition, behavioral or psychiatric disorder (including active suicidal ideation), or history or presence of another neurological disorder or surgical history that might affect the subject’s safety and/or interfere with the conduct of the study in the opinion of the Investigator. 13.A current electrocardiogram (ECG) with clinically significant deviation(s) from normal, or clinically significant physical examination findings, as determined by the Investigator at screening. 14.Any current clinically significant laboratory abnormality as determined by the Investigator at screening. 15.Is a female subject who is pregnant, nursing, or lactating. 16.A positive urine drug screen for benzodiazepines or drugs of abuse, a positive alcohol test, a history of substance abuse including alcohol abuse, or unwillingness to refrain from consuming alcohol during the study (if the subject takes prescribed amphetamines, a positive result for amphetamines will not exclude the subject). 17.Treatment with any central nervous system sedating agents, including, but not limited to, benzodiazepines, non-benzodiazepine anxiolytics/ hypnotics/sedatives, neuroleptics, opioids, barbiturates, phenytoin, ethosuximide, or the monocarboxylate transporter (MCT) inhibitor valproate, within 2 weeks prior to enrollment (Day 1) (discontinuation for the purpose of study enrollment is permitted only if considered safe by the Investigator and approved by the Medical Monitor). 18.Treatment with an antidepressant for cataplexy, if the withdrawal of the antidepressant during cross-titration with JZP-258 might be unsafe due to prior history of depression. 19.Current treatment with oral isotretinoin. 20.Received any investigational drug within 30 days or 5 half-lives (whichever is longer) before the Screening Visit. 21.Allergy or sensitivity to malic acid, sucralose or ingredients in the study drug formulation or placebo. 22.Unsafe for the subject to receive placebo treatment for 2 weeks, in the opinion of the Investigator. Open Label 1.Meet Exclusion Criteria 1 through 19 from the Main Study at Visits 18 and 19. 2.Received any investigational drug (with the exception of JZP 258) within 30 days or 5 half-lives (whichever is longer) before the Screening Visit. 3.Allergy or sensitivity to malic acid, sucralose or ingredients in the study drug formulation.
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in weekly number of cataplexy attacks from the two weeks of the Stable-Dose Period to the two weeks of the Double-Blind Randomized-Withdrawal Period |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
End of stable-dose period to end of double- blind randomized-withdrawal period (2 weeks) |
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E.5.2 | Secondary end point(s) |
• Change in the Epworth Sleepiness Scale (ESS) score from the end of the Stable- Dose Period to the end of the Double-Blind Randomized-Withdrawal Period. • PGIc for narcolepsy overall at the end of the Double-Blind Randomized-Withdrawal Period. • CGIc for narcolepsy overall at the end of the Double-Blind Randomized-Withdrawal Period. • Change in QoL (SF-36) from the end of the Stable-Dose Period to the end of the Double-Blind Randomized-Withdrawal Period. • Change in QoL (EuroQol 5 Dimensions Self-Report Questionnaire) from the end of the Stable-Dose Period to the end of the Double-Blind Randomized- Withdrawal Period. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of stable-dose period to end of double-blind randomized-withdrawal period (2 weeks) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
followed by a 24-week Open-Label Extension study |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Belgium |
Croatia |
Czech Republic |
Denmark |
Finland |
France |
Germany |
Italy |
Netherlands |
Poland |
Spain |
Sweden |
Switzerland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |